Objective: The role of homeobox A3 (HOXA3) in cancer progression is gaining prominence, however, to date, no studies have investigated its regulatory function in oral cancer. In this study, we explored the role of HOXA3 through epigenetic mechanisms.
Methods: Clinical samples were collected from 25 potentially malignant oral lesions and 50 oral squamous cell carcinoma (OSCC) patients, categorized into low-stage and high-stage tumors. The promoter activity of HOXA3 was determined through cloning and luciferase assays. CpG methylation patterns across the gene were identified using methyl-capture sequencing. Gene expression was analyzed using RT‒qPCR. The Survminer R package was used to assess the clinical significance of 3' UTR methylation associated with overall survival. RNA‒RNA interactions were analyzed using RNAInter and TargetScan v8.0.
Results: HOXA3 expression was upregulated in dysplasia and downregulated in advanced cancer stages, showing an inverse correlation with promoter methylation, suggesting epigenetic regulation by DNA methylation. Hypermethylation of the 3' UTR was associated with poor overall survival in advanced stages. Long noncoding RNAs and microRNAs may post-transcriptionally modulate HOXA3 in oral carcinogenesis.
Conclusion: CpG-specific hypermethylation in the 3' UTR may serve as a potential biomarker in OSCC.
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